Synthesis and opioid receptor binding affinities of 2-substituted and 3-aminomorphinans: ligands for mu, kappa, and delta opioid receptors.

摘要: The phenolic group of the potent mu and kappa opioid morphinan agonist/antagonists cyclorphan butorphan was replaced by phenylamino benzylamino groups including compounds with para-substituents in benzene ring. These are highly ligands, e.g., p-methoxyphenylaminocyclorphan showing a K(i) 0.026 nM at receptor 0.03 receptor. Phenyl carbamates phenylureas were synthesized investigated. Selective o-formylation levorphanol achieved. This reaction opened way to large set 2-substituted 3-hydroxymorphinans, 2-hydroxymethyl-, 2-aminomethyl-, N-substituted 2-aminomethyl-3-hydroxymorphinans. Bivalent ligands bridged 2-position also connected secondary tertiary aminomethyl groups, amide bonds, hydroxymethylene respectively. Although most morphinans showed considerably lower affinities compared their parent compounds, bivalent ligand approach led significantly higher univalent morphinans.